Methods

The present study extended this analysis to a broader range of signaling pathway components
downstream of the B cell receptor (BCR) in European Americans and African Americans
using a subset of donors from the previously analyzed cohort of 60 healthy donors.
Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular
readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors
[5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males].

Results

Analysis of BCR signaling activity in European American and African American PBMC
samples revealed that, compared to the European American donors, B cells from African
Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components,
including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K
pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-κB pathway (NF-κB).
In addition to differences in the magnitude of anti-IgD-induced pathway activation,
racial differences in BCR signaling kinetic profiles were observed. Further, the frequency
of IgD+ B cells differed by race and strongly correlated with BCR pathway activation.
Thus, the race-related difference in BCR pathway activation appears to be attributable
at least in part to a race-associated difference in IgD+ B cell frequencies.